Measuring von Willebrand factor (VWF) activity is essential for the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. A new automated chemiluminescent immunoassay VWF activity has recently become commercially available (HemosIL AcuStar von Willebrand Factor Ristocetin Cofactor Activity). The main objective of this study was to evaluate this new method and to compare it with the VWF:RCo assay as the reference method. We studied 91 samples, 18 healthy volunteers samples and 73 samples from patients (VWF:RCo level <50 IU dL(-1) ): 29 type 1 VWD, 13 type 2A, 5 type 2B, 5 type 2M, 3 type 2N, 5 type 3, 4 type 3 under treatment, 5 type 3 carriers and 4 samples with other pathologies. The HemosIL AcuStar VWF:RCo assay was 96% sensitive and 100% specific for detecting VWF abnormalities. The good analytical performance, and the sensitivity and specificity of HemosIL AcuStar VWF:RCo to detect VWF deficiency renders it a suitable method for VWD screening.

Head-on comparative studies of factor IX (FIX) concentrates performed under standardized conditions are rarely conducted regardless of being a valuable instrument guiding health care providers towards better informed and cost-effective decisions. This study is an extension of a multicentre study that assessed the efficacy, safety and pharmacokinetics (PK) of AlphaNine(®) in 25 previously treated patients with severe haemophilia B (FIX:C ≤ 2%). After a washout period ≥ 7 days following the last PK performed with AlphaNine(®) after a dose of 65-75 IU kg(-1) , an identical PK study was performed with BeneFIX(®) on 22 of the same patients. Venous blood samples for analysis were taken at baseline and at 0.25, 0.5, 1, 3, 6, 9, 24, 48, 72 and 74 h post infusion. The outcomes of the comparison of the PK parameters were as follows: Mean (± SD) in vivo recovery (IVR) was 1.3 ± 0.4 IU dL(-1) per IU kg(-1) for AlphaNine(®) and 1.0 ± 0.3 IU dL(-1) per IU kg(-1) for BeneFIX(®) (P < 0.01). Mean terminal half-life, mean residence time, area under the curve, clearance and volume of distribution of BeneFIX(®) were 36.0 ± 12.8 h, 39.3 ± 13.9 h, 1631 ± 467 IU h dL(-1) , 0.046 ± 0.01 dL kg(-1) min(-1) and 1.75 ± 0.52 mL kg(-1) respectively. These values were not significantly different to those observed in AlphaNine(®), although BeneFIX(®) displayed higher than expected IVR values and lower than expected clearance values. In conclusion, AlphaNine(®) showed a comparable half-life, but an IVR significantly higher than that of BeneFIX(®). This dissimilarity may have implications on dosing requirements for on-demand treatment regimes affecting optimal resource allocation.

Background: Prophylaxis with recombinant factor VIII (rFVIII) is considered the optimal treatment for severe or moderate haemophilia A (HA). Bleeding into joints determines a proportional chronic joint damage to its frequency and severity. Knowledge of the individual's pharmacokinetics (PK) using Bayesian analysis helps to individualize prophylaxis therapy with recombinant factor VIII (rFVIII) in severe or moderate haemophilia A (HA) and minimize the risk of bleeding, extracting only 2-3 samples. Methods Retrospective study in HA patients with rFVIII (Advate®) prophylaxis from January 2014 to May of 2016. Bayesian model (myPKFit®) was employed to perform an individual PK profile using the retrospective data of rFVIII levels. PK parameters analyzed were: clearance (Cl); steady state volume (Vss); plasma half-life (t1/2); and time to reach rFVIII levels <1% (T1%). Intraindividual and interindividual coefficients of variation (CV) of the t1/2 were calculated. Besides, Kruskal-Wallis test (R® version 3.1.2) was employed in comparisons between t1/2 and clinical variables: annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), Gilbert score (GS), Pettersson scale (PS) & lower extremity affected joints detected by NMR. Results Nineteen patients were analyzed, with a mean age of 32 years (SD: 11.3; range 11-46) and 86 PK monitoring (4.5 per patient). Two patients with <15 years were excluded because t1/2 was lower than adult patients. The mean PK values in adult patients were: Cl 2.9 (0.40) mL/h/kg; Vss 50.0 (<0.001) ml/kg; t1/2 14.1 (2.1) h; and T1% 74.4 (14.4) h. The mean intraindividual CV in t1/2 was 3.6% (SD 0.02; range 0.3-6.6), whereas interindividual CV was 14.8%. We categorized t1/2 in short (<p25: 12.3 h), normal (p25-p75) and long (>p75 14.4 h), with average age of 19.5; 39.4 & 35.8 years, respectively. We detected significant differences between t1/2 and median values of joint state, but not in ABR and AJBR. The mean values of joint scores were: PS (5.5, 22.1; 17; p=0.028), GS (1, 25.9, 17.6; p= 0,008) and NMR (1.2, 2.6, 2.0; p=0.042) for short, normal and long t1/2, respectively. The limited number of patients only allows observe significant differences in patients with short t1/2, patients that also have significantly lower age (p=0.007). The younger age of these patients also justifies the lower joint damage observed. After excluding two patients <15 years significant differences in the scores of the joint state disappeared, showing that age could be a confounding variable. Conclusion PK monitoring showed a low intraindividual variability in t1/2, but significant interindividual CV. Age could modify PK parameters, so it should be assessed in an integrated manner with other clinical variables. Bayesian estimate with MyPKFit® allows know the PK profile of each patient and could be a useful tool to individualize prophylaxis adjusting by the physical activity and the bleeding pattern. We are performing a personalized one-year program to identify and treat the specific causes of poor bleeding control in prophylaxis therapy, and these are our preliminary results. Acknowledgments: This study will be supported by Baxalta grant "H15-29403". Disclosures Cid: Baxalta Innovations GmbH, now part of Shire: Other: Investigator Clinical Studies.